The overall goal of the proposed studies is to establish the feasibility of developing therapies for brain cancers such as glioblastoma multiforme from the schweinfurthin family of antiproliferative agents. These agents are highly toxic to CNS derived tumor cell lines in vitro and more importantly appear to exhibit this activity via a novel cellular target(s). The schweinfurthins also contain chemical functional groups which should facilitate cerebrovascular barrier penetration, a very important aspect of drugs aimed at treating primary brain cancers. Phase One of these studies is comprised of three narrowly focused aims directed at proving the feasibility of finding advancing? a therapeutic lead from this family: These aims include: 1) synthesis of analogs of the schweinfurthins bearing functional groups designed to improve the "drug-like" nature of the compounds; 2) improvement of the published synthesis of the hexahydroxanthene core of the 3-deoxyschweinfurthin motif to allow for more efficient and safe production of larger quantities of material for Phase Two studies; and 3) biological studies aimed at elucidation of the cellular or molecular target of the schweinfurthins. These aims will allow a decision to be made about feasibility of studying these drugs further in pre-clinical animal models as part of Phase Two, and ultimately of bringing drugs based on this unique and potent family of compounds into use against brain cancer. [unreadable] [unreadable] [unreadable]